Spectroscopic Imaging at 4T: A Drug Challenge Study

Not Applicable

Terminated

Conditions: AOD Effects and Consequences

Interventions: Other: Placebo
Drug: Alprazolam
Drug: Dextroamphetamine

Registration Number: NCT01577706

Lead Sponsor: Mclean Hospital

Brief Summary: An advanced technique for rapid magnetic resonance proton spectroscopic imaging (1H-MRSI) will be employed in a drug challenge study in healthy volunteers to spatially map and measure acute changes in the brain chemicals GABA, glutamate and glutamine after administration of a drug. Three condition will be tested in a double-blind fashion, i)depressant, ii)stimulant, iii)placebo. It is hypothesized that unique and reproducible spatial and directional metabolic response patterns will be observed, unique to each condition within the brain.

Detailed Description: Proton magnetic resonance spectroscopy (1H MRS) is a powerful tool for assessing neurochemistry non-invasively in vivo. However, the primary shortcoming in most studies is the lack of spatial coverage afforded by the typical single-voxel design. Limits on participant tolerance and financial resources restrict single-voxel studies to an examination of one or two carefully chosen voxels per scan, thus inadequately addressing the question of focal vs. global pathophysiology. A secondary shortcoming is that most studies report on either GABA or glutamate-glutamine (Glu-Gln) due to the technically demanding spectral-editing techniques that must be implemented in order to resolve and quantify those metabolites with any accuracy.

1H MRS imaging (MRSI) can partially overcome these limitations by providing a global picture of brain chemistry rather than just the focal snapshot afforded by the single-voxel design. However, the scan time necessary for collecting enough data for adequate spatial resolution and signal-to-noise, particularly if also using specialized spectral-editing techniques, is still too lengthy. We recently developed a method that combines Spectroscopic Imaging with the MEGAPRESS-based difference-editing acquisition for optimal GABA detection as well as for optimal detection of Glu and Gln. This MEGACSI sequence will permit us to obtain the maximum amount of neurochemical information in a clinically sound scan time, while using the current state-of-the-art MRS editing methods for optimal detection of GABA, Glu, and Gln.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 7

Inclusion Criteria

Participants will be male volunteers between the ages of 21-45
Non-smoking participants are preferred, but will admit those who smoke less than 5 cigarettes per day
Participants must be able to read screening materials including consent form and give informed consent

Exclusion Criteria

Participants cannot meet DSM-IV criteria for lifetime and/or current mood, anxiety, psychotic, and alcohol/drug use disorders as identified by the SCID
Participants cannot be taking any prescription medication (except oral contraceptives, certain short-term anti-fungal agents, and some topical creams for dermal conditions) or nutritional supplements
Participants cannot be taking any psychotropic medications
Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
Participants cannot have any conditions that are contraindicated for MRI
Participants cannot have a family history of alcoholism
Participants cannot have any abnormal blood chemistries/urinalysis results or any other medical condition that may affect drug disposition (e.g., Hepatitis C)
Participants cannot have current or past cardiac problems, and they also cannot have a family history of sudden death or ventricular arrhythmia
Participants who, in the investigators' judgment, will not likely be able to comply with the study protocol.
Participants cannot have any clinically significant findings in the structural anatomic brain scans (per the MRI report read by a board-certified radiologist).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo (P)	Placebo	Placebo gel-capsule, single-dose, 1-day
Alprazolam (A)	Alprazolam	Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day
Dextroamphetamine (D)	Dextroamphetamine	Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day

Primary Outcome Measures

Name	Time	Method
Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Right Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Right Temporal: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Left Temporal: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Right Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Left Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge	from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)	The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint